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윤재석,구선미,이택형,송윤정,성선화,김영훈,차혜진,한경문,신지순,오호경,정기경,안치영,박혜경,김형수 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) 3ε, CD3γ, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.
윤재석,김소영,윤경식,신희정,정호상,정혜주,김영훈,신지순,차혜진,한경문,현승하,이택형,박혜경,김형수 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.12
Astemizole, a non-sedating histamine H1 receptorblocker, is widely known to cause cardiac arrhythmia,which prolongs the QT interval. However, the precisemolecular mechanism involved in antihistamine-inducedcardiovascular adverse effects other than hERG channelinhibition is still unclear. In this study, we used DNAmicroarray analysis to detect the mechanisms involved inlife-threatening adverse effects caused by astemizole. Ratprimary cardiomyocytes were treated with various concentrationsof astemizole for 24 h and the correspondingcell lysates were analyzed using a DNA microarray. Astemizole altered the expression profiles of genesinvolved in calcium transport/signaling. Using qRT-PCRanalysis, we demonstrated that, among those genes, p21(Cdc42/Rac)-activated kinase 1 (pak1) mRNA was downregulatedby treatment with terfenadine and astemizole. Astemizole also reduced pak1 protein levels in rat cardiomyocytes. In addition, astemizole decreased pak1mRNA and protein levels in H9c2 cells and induced anincrease in cell surface area (hypertrophy) and cytotoxicity. Fingolimod hydrochloride (FTY720), a pak1 activator,inhibited astemizole-induced hypertrophy and cytotoxicityin H9c2 cells. These results suggest that antihistamine-inducedcardiac adverse effects are associated with pak1expression and function.